ArticleInternational journal of biological sciences2018
Chemical and genetic inhibition of STAT3 sensitizes hepatocellular carcinoma cells to sorafenib induced cell death.
Article in International journal of biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Multi-omics and machine learning refine HCC molecular subtypes and prognosis based on liquid-liquid phase separation related genes.Scientific reports · 2025Article
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Coordinated gene expression within sustained STAT3-associated chromatin conformations contributes to hepatocellular carcinoma progression.Cancer communications (London, England) · 2025Article
- Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity.Cancer gene therapy · 2025Article
- Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.Molecular and cellular biochemistry · 2025Review
- Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.Acta pharmacologica Sinica · 2024Article
- Network pharmacology prediction and experiment validation of anti-liver cancer activity of Curcumae Rhizoma and Hedyotis diffusa Willd.Annals of medicine and surgery (2012) · 2024Article
- Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.Journal of Cancer · 2024Article
- IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis.Frontiers in immunology · 2024Article
- Venetoclax Overcomes Sorafenib Resistance in Acute Myeloid Leukemia by Targeting BCL2.Biology · 2023Article
- GPRC5A regulates proliferation and oxidative stress by inhibiting the STAT3/Socs3/c-MYC pathway in hepatocellular carcinoma.Journal of clinical biochemistry and nutrition · 2023Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Ultrasensitive quantification of trace amines based onJournal of pharmaceutical analysis · 2023Article
- Article
- Single-cell and genetic multi-omics analysis combined with experiments confirmed the signature and potential targets of cuproptosis in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2023Article
- Screening and Verification of Key Ubiquitination Genes Related to Immune Infiltration in Stage III/IV Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Article
- Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models.Journal of ginseng research · 2022Article
- The JAK/STAT signaling pathway: from bench to clinic.Signal transduction and targeted therapy · 2021Review
- Article
- Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.Cancer cell international · 2021Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) has become the second leading cause of cancer related death, with an increasing death rate in recent years. For advanced HCC, sorafenib is the first-line FDA approved drug, with no more than 3 months' overall survival advantage. Recently, a novel strategy has been proposed to improve sorafenib efficacy through enhancing the ability of sorafenib to induce cell death. STAT3 plays a key role in cancer development and recurrence by promoting cell proliferation, survival and immune evasion through its well-established function as a transcription factor in cancer. Notably, STAT3 transcription activity, indicated by its phosphorylation on Y705 is heterogeneous in different liver cancer cell lines. And sorafenib attenuates STAT3 phosphorylation on Y705. However, the role of STAT3 in sorafenib induced cell death is still largely unknown. Here, we show that liver cancer cells also exhibit heterogeneous sensitivities to sorafenib induced cell death, which co-relates with the STAT3-Y705 phosphorylation levels and JAK1/2 expression levels in Hep3B, Huh7 and HepG2 cells. Furthermore, overexpression or knockdown of STAT3 could switch HCC cells between resistant and sensitive to sorafenib induced cell death, which could be partially due to its regulation on Mcl-1, an anti-apoptotic protein. Finally, both inhibitors of STAT3 SH2 domain (S3i-201) or STAT3 upstream kinases JAKs (JAK inhibitor I) could synergistically enhance sorafenib induced cell death. Taken together, these data strongly suggest that STAT3 is not only a downstream effector of sorafenib, but also a key regulator of cellular sensitivity to sorafenib induced cell death, which provide support for the notion to develop STAT3-targeting drugs to improve clinical efficacy of sorafenib in liver cancer.
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